PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery
Abstract
We investigated the in vitro and in vivo properties of DNA/transferrin-polyethylenimine (800 kDa) complexes before and after covalent coupling of poly(ethylene glycol) (PEG). Upon incubation with plasma, the positively charged non-PEGylated DNA complexes form aggregates. Plasma proteins such as IgM, fibrinogen, fibronectin and complement C3 were found to bind to non-PEGylated DNA complexes. At DNA concentrations relevant for in vivo gene delivery a strong aggregation of erythrocytes was also observed. PEGylation of the complexes strongly reduces plasma protein binding and erythrocyte aggregation. Furthermore, PEGylated complex size was stabilized and had a reduced surface charge. Prolonged circulation in the blood of the PEGylated complexes was also observed when injected intravenously. In tumor bearing mice, application of non-PEGylated complexes through the tail vein resulted in reporter gene expression in tail and lung, but severe toxicity was observed in some mice. In contrast, PEGylated complexes mediated reporter gene transfer to the tumor without significant toxicity.
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PEGylation is most commonly used strategy to reduce opsonization and minimize clearance by RES, may be applicable for non-viral vectors-mediated CRISPR/Cas9 delivery.
“PEGylation, the most commonly used strategy to reduce the opsonization and minimize the clearance by RES, may also be applicable for non-viral vectors-mediated CRISPR/Cas9 delivery [144, 145].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [144]
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- Authors
- Ogris, M., Brunner, S., Schüller, S., Kircheis, R., & Wagner, E.
- Affiliations
- University of Vienna (AT)
- Boehringer Ingelheim (Austria) (AT)
- Venue
- Gene Therapy
- Published
- 1999-04-01
- Volume
- 6
- Issue
- 4
- Pages
- 595-605
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- OpenAlex
- W2074870430
- Cited by
- 1,178
- References
- 49
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 14 · 2023: 14 · 2022: 19 · 2021: 21 · 2020: 27 · 2019: 38 · 2018: 30 · 2017: 42 · 2016: 56 · 2015: 49 · 2014: 52 · 2013: 71 · 2012: 70
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- PEGylation, transferrin, polyethyleneimine, DNA complexes, systemic gene delivery, plasma protein binding, erythrocyte aggregation, blood circulation, surface charge, toxicity, non-viral vectors
- MeSH terms
- Animals, Biophysics, Blood Proteins, Cell Line, DNA, Erythrocytes, Female, Genetic Vectors, Luciferases, Mice, Inbred Strains, Neoplasm Transplantation, Neoplasms, Experimental, Polyethylene Glycols, Polyethyleneimine, Transfection, Genetic Therapy, Gene Expression, Mice, Biophysical Phenomena
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